Research is proposed in the following areas: 1. Thermodynamic studies will be carried out of the factors which control or affect the in vitro self-assembly of microtubules from purified brain tubulin. Particular attention will be paid to the formation of possible intermediates and the effect of ligands. 2. The interactions of anti-cancer drugs with tubulin and their effects on tubulin self-association will be examined on the molecular level. 3. The effects of solvent constituents on microtubule formation and stability will be investigated, with particular emphasis on the specific and non-specific interactions which occur between solvent components and protein. BIBLIOGRAPHIC REFERENCES: Effects of Solvents on In Vitro Microtubule Formation, J.C. Lee and S.N. Timasheff, ABS., Amer. Chem. Soc. 170th meeting, Chicago, August 1975. Interaction of Vinblastine with Calf Brain Microtubule Protein, J.C. Lee, D. Harrison, and S.N. Timasheff, J. Biol. Chem. (1975) in press.